Spencer T A, Gayen A K, Phirwa S, Nelson J A, Taylor F R, Kandutsch A A, Erickson S K
J Biol Chem. 1985 Nov 5;260(25):13391-4.
Previously we showed that 24(S),25-epoxycholesterol is formed from acetate, via squalene 2,3(S),22(S),23-dioxide and 24(S),25-oxidolanosterol, during the normal course of cholesterol biosynthesis in S10 rat liver homogenate (Nelson, J. A., Steckbeck, S. R., and Spencer, T. A. (1981) J. Biol. Chem. 256, 1067-1068; Nelson, J. A., Steckbeck, S. R., and Spencer, T. A. (1981) J. Am. Chem. Soc. 103, 6974-6975). Herein we demonstrate that the nonsaponifiable extract from human liver tissue contains 24(S),25-epoxycholesterol in an amount approximately 10(-3) relative to cholesterol. We show that 24(S),25-epoxycholesterol, like many other oxygenated sterols, represses hydroxymethylglutaryl-CoA reductase activity in cultured cells and binds to the cytosolic oxysterol-binding protein. Furthermore, we show that this epoxide is not rapidly metabolized in cultured cells. These results suggest that 24(S),25-epoxycholesterol may participate in the regulation of hepatic cholesterol metabolism in vivo.
先前我们表明，在S10大鼠肝脏匀浆中胆固醇生物合成的正常过程中，24(S),25-环氧胆固醇是由乙酸盐经角鲨烯2,3(S),22(S),23-二氧化物和24(S),25-氧化羊毛甾醇形成的（尼尔森，J.A.，斯特克贝克，S.R.，和斯宾塞，T.A.（1981年）《生物化学杂志》256，1067 - 1068；尼尔森，J.A.，斯特克贝克，S.R.，和斯宾塞，T.A.（1981年）《美国化学会志》103，6974 - 6975）。在此我们证明，人肝脏组织的不皂化物提取物中24(S),25-环氧胆固醇的含量相对于胆固醇约为10⁻³。我们表明，24(S),25-环氧胆固醇与许多其他氧化甾醇一样，可抑制培养细胞中羟甲基戊二酰辅酶A还原酶的活性，并与胞质氧化甾醇结合蛋白结合。此外，我们表明这种环氧化物在培养细胞中不会快速代谢。这些结果表明，24(S),25-环氧胆固醇可能参与体内肝脏胆固醇代谢的调节。
